tbuckley/cabot-search huggingface dataset:
Prevalence and Prognostic Significance of Bradyarrhythmias in Patients Screened for Atrial Fibrillation vs Usual Care
Authors: Søren Zöga Diederichsen, Lucas Yixi Xing, Diana My Frodi, Emilie Katrine Kongebro, Ketil Jørgen Haugan, Claus Graff, Søren Højberg, Derk Krieger, Axel Brandes, Lars Køber, Jesper Hastrup Svendsen
Journal: JAMA Cardiology (2023)

There is increasing interest in heart rhythm monitoring and technologies to detect subclinical atrial fibrillation (AF), which may lead to incidental diagnosis of bradyarrhythmias.To assess bradyarrhythmia prevalence and prognostic significance in persons screened for AF using implantable loop recorder (ILR) compared with unscreened persons.This was a post hoc analysis of the Implantable Loop Recorder Detection of Atrial Fibrillation to Prevent Stroke (LOOP) randomized clinical trial, which took place in 4 sites in Denmark. Participants were 70 years or older without known AF but diagnosed with at least 1 of the following: hypertension, diabetes, heart failure, or prior stroke. Participants were recruited by letter invitation between January 31, 2014, and May 17, 2016. The median (IQR) follow-up period was 65 (59-70) months. Analysis took place between February and June 2022.ILR screening for AF with treatment of any bradyarrhythmia left to the discretion of the treating physician (ILR group) vs usual care (control group).Adjudicated bradyarrhythmia episodes, pacemaker implantation, syncope, and sudden cardiovascular death.A total of 6004 participants were randomized (mean [SD] age, 75 [4.1] years; 2837 [47.3%] female; 5444 [90.7%] with hypertension; 1224 [20.4%] with prior syncope), 4503 to control and 1501 to ILR. Bradyarrhythmia was diagnosed in 172 participants (3.8%) in the control group vs 312 participants (20.8%) in the ILR group (hazard ratio [HR], 6.21 [95% CI, 5.15-7.48]; P < .001), and these were asymptomatic in 41 participants (23.8%) vs 249 participants (79.8%), respectively. The most common bradyarrhythmia was sinus node dysfunction followed by high-grade atrioventricular block. Risk factors for bradyarrhythmia included higher age, male sex, and prior syncope. A pacemaker was implanted in 132 participants (2.9%) vs 67 (4.5%) (HR, 1.53 [95% CI, 1.14-2.06]; P < .001), syncope occurred in 120 (2.7%) vs 33 (2.2%) (HR, 0.83 [95% CI, 0.56-1.22]; P = .34), and sudden cardiovascular death occurred in 49 (1.1%) vs 18 (1.2%) (HR, 1.11 [95% CI, 0.64-1.90]; P = .71) in the control and ILR groups, respectively. Bradyarrhythmias were associated with subsequent syncope, cardiovascular death, and all-cause death, with no interaction between bradyarrhythmia and randomization group.More than 1 in 5 persons older than 70 years with cardiovascular risk factors can be diagnosed with bradyarrhythmias when long-term continous monitoring for AF is applied. In this study, ILR screening led to a 6-fold increase in bradyarrhythmia diagnoses and a significant increase in pacemaker implantations compared with usual care but no change in the risk of syncope or sudden death.
Is Faster Transport Time Really Associated With Decreased Firearm Injury Mortality?
Authors: Nicolas Cazes, Aurélien Renard, Cédric Boutillier Du Retail
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Intrathymic AAV delivery results in therapeutic site-specific integration at TCR loci
Authors: Andrea Calabria, Carlo Cipriani, Giulio Spinozzi, Laura Rudilosso, Simona Esposito, Fabrizio Benedicenti, Alessandra Albertini, Marie Pouzolles, Mirko Luoni, Serena Giannelli, Vania Broccoli, Mickael Guilbaud, Oumeya Adjali, Naomi Taylor, Valérie S. Zimmermann, Eugenio Montini, Daniela Cesana
Journal: Blood (2023)

Adeno-associated Viral vectors (AAVs) have been successful exploited in gene therapy applications for the treatment of several genetic disorders. AAV is considered an episomal vector but it has been shown to integrate within the host-cell genome following generation of double-strand DNA breaks or nicks. While AAV integration raises some safety concerns, it can also provide therapeutic benefit; the direct intrathymic injection of an AAV harboring a therapeutic transgene results in integration in T cell progenitors and long-term T cell immunity. To assess the mechanisms of AAV integration, we retrieved and analyzed hundreds of AAV integration sites from lymph node-derived mature T-cells as compared to liver and brain tissue from treated mice. Notably, we found that while AAV integrations in the liver and brain were distributed across the entire mouse genome, &amp;gt;90% of the integrations in T-cells were clustered within the T cell receptor α, β and γ genes. More precisely, the insertion mapped to DNA breaks created by the enzymatic activity of recombination activating genes (RAG) during V(D)J recombination. Our data indicate that RAG activity during T-cell receptor maturation induces a site-specific integration of AAV genomes and opens new therapeutic avenues for achieving long-term AAV-mediated gene transfer in dividing cells.
Factors Associated With Primary Care Physician Decision-making When Making Medication Recommendations vs Surgical Referrals
Authors: Anusha Naik, Solomiya Syvyk, Jason Tong, Chris Wirtalla, Frances K. Barg, Carmen E. Guerra, Shivan J. Mehta, Richard Wender, Raina M. Merchant, Rachel R. Kelz
Journal: JAMA Network Open (2023)

Importance Although objective data are used routinely in prescription drug recommendations, it is unclear how referring physicians apply evidence when making surgeon or hospital recommendations for surgery. Objective To compare the factors associated with the hospital or surgeon referral decision-making process with that used for prescription medication recommendations. Design, Setting, and Participants This qualitative study comprised interviews conducted between April 26 and May 18, 2021, of a purposive sample of 21 primary care physicians from a large primary care network in the Northeast US. Main Outcomes and Measures Main outcomes were the factors considered when making prescription medication recommendations vs referral recommendations to specific surgeons or hospitals for surgery. Results All 21 participant primary care physicians (14 women [66.7%]) reported use of evidence-based decision support tools and patient attributes for prescription medication recommendations. In contrast, for surgeon and hospital referral recommendations, primary care physicians relied on professional experience and training, personal beliefs about surgical quality, and perceived convenience. Primary care physicians cited perceived limitations of existing data on surgical quality as a barrier to the use of such data in the process of making surgical referrals. Conclusions and Relevance As opposed to the widespread use of objective decision support tools for guidance on medication recommendations, primary care physicians relied on subjective factors when making referrals to specific surgeons and hospitals. The findings of this study highlight the potential to improve surgical outcomes by introducing accessible, reliable data as an imperative step in the surgical referral process.
“KEAP”ing Alveolar Macrophage Mitochondria Content in Chronic Obstructive Pulmonary Disease
Authors: Suzanne M. Cloonan
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"‘KEAP’ing Alveolar Macrophage Mitochondria Content in COPD." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
FDA Approves First Oral Treatment for Kidney Disease–Induced Anemia
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<scp>CU06</scp>‐1004 alleviates vascular hyperpermeability in a murine model of hereditary angioedema by protecting the endothelium
Authors: Sunghye Lee, Yeomyeong Kim, Ye‐Seul Kim, Haiying Zhang, Minyoung Noh, Young‐Guen Kwon
Journal: Allergy (2023)

Over-release of the vasoactive peptide bradykinin (BK) due to mutation in the SERPING1 gene is the leading cause of hereditary angioedema (HAE). BK directly activates endothelial cells and increases vascular permeability by disrupting the endothelial barrier, leading to angioedema affecting face, lips, extremities, gastrointestinal tract, and larynx. Although various pharmacological treatment options for HAE became available during the last decade, they are presently limited and pose a major economic burden on patients. To identify additional therapeutic options for HAE, we evaluated the effect of CU06-1004, an endothelial dysfunction blocker, on BK-induced vascular hyperpermeability and the HAE murine model.To investigate the effect of CU06-1004 on BK-induced vascular hyperpermeability in vivo, we pre-administrated WT mice with the drug and then induced vascular leakage through intravenous injection of BK and observed vascular alternation. Then, SERPING1 deficient mice were used for a HAE murine model. For an in vitro model, the HUVEC monolayer was pre-treated with CU06-1004 and then stimulated with BK.Bradykinin disrupted the endothelial barrier and formed interendothelial cell gaps, leading to hyperpermeability in vivo and in vitro. However, CU06-1004 treatment protected the endothelial barrier by suppressing Src and myosin light chain activation via BK and alleviated hyperpermeability.Our study shows that CU06-1004 oral administration significantly reduced vascular hyperpermeability in the HAE murine model by protecting the endothelial barrier function against BK stimulation. Therefore, protecting endothelium against BK with CU06-1004 could serve as a potential prophylactic/therapeutic approach for HAE patients.
Contemporary Outcomes of Elective Parastomal Hernia Repair in Older Adults
Authors: Ryan Howard, Farizah Rob, Jyothi Thumma, Anne Ehlers, Sean O’Neill, Justin B. Dimick, Dana A. Telem
Journal: JAMA Surgery (2023)

Importance Parastomal hernia is a challenging complication following ostomy creation; however, the incidence and long-term outcomes after elective parastomal hernia repair are poorly characterized. Objective To describe the incidence and long-term outcomes after elective parastomal hernia repair. Design, Setting, and Participants Using 100% Medicare claims, a retrospective cohort study of adult patients who underwent elective parastomal hernia repair between January 1, 2007, and December 31, 2015, was performed. Logistic regression and Cox proportional hazards models were used to evaluate mortality, complications, readmission, and reoperation after surgery. Analysis took place between February and May 2022. Exposures Parastomal hernia repair without ostomy resiting, parastomal hernia repair with ostomy resiting, and parastomal hernia repair with ostomy reversal. Main Outcomes and Measures Mortality, complications, and readmission within 30 days of surgery and reoperation for recurrence (parastomal or incisional hernia repair) up to 5 years after surgery. Results A total of 17 625 patients underwent elective parastomal hernia repair (mean [SD] age, 73.3 [9.1] years; 10 059 female individuals [57.1%]). Overall, 7315 patients (41.5%) underwent parastomal hernia repair without ostomy resiting, 2744 (15.6%) underwent parastomal hernia repair with ostomy resiting, and 7566 (42.9%) underwent parastomal hernia repair with ostomy reversal. In the 30 days after surgery, 676 patients (3.8%) died, 7088 (40.2%) had a complication, and 1740 (9.9%) were readmitted. The overall adjusted 5-year cumulative incidence of reoperation was 21.1% and was highest for patients who underwent parastomal hernia repair with ostomy resiting (25.3% [95% CI, 25.2%-25.4%]) compared with patients who underwent parastomal hernia repair with ostomy reversal (18.8% [95% CI, 18.7%-18.8%]). Among patients whose ostomy was not reversed, the hazard of repeat parastomal hernia repair was the same for patients whose ostomy was resited vs those whose ostomy was not resited (adjusted hazard ratio, 0.93 [95% CI, 0.81-1.06]). Conclusions and Relevance In this study, more than 1 in 5 patients underwent another parastomal or incisional hernia repair within 5 years of surgery. Although this was lowest for patients who underwent ostomy reversal at their index operation, ostomy resiting was not superior to local repair. Understanding the long-term outcomes of this common elective operation may help inform decision-making between patients and surgeons regarding appropriate operative approach and timing of surgery.
Association of Cardiovascular Health With Risk of Clinically Relevant Depressive Symptoms
Authors: Thomas T. van Sloten, Eugénie Valentin, Rachel E. Climie, Xavier Jouven, Cedric Lemogne, Marcel Goldberg, Marie Zins, Jean-Philippe Empana
Journal: JAMA Psychiatry (2023)

Cardiovascular health may be used for prevention of depressive symptoms. However, data on the association of cardiovascular health across midlife with depressive symptoms are lacking.
In Vivo Stable Allogenic Cartilage Regeneration in a Goat Model Based on Immunoisolation Strategy Using Electrospun Semipermeable Membranes
Authors: Yingying Huo, Baoshuai Bai, Rui Zheng, Yuyan Sun, Yao Yu, Xin Wang, Hong Chen, Yujie Hua, Yixin Zhang, Guangdong Zhou, Xiaoyun Wang
Journal: Advanced Healthcare Materials (2023)

Tissue engineering is a promising strategy for cartilage defect repair. However, autologous cartilage regeneration is limited by additional trauma to the donor site and a long in vitro culture period. Alternatively, allogenic cartilage regeneration has attracted attention because of the unique advantages of an abundant donor source and immediate supply, but it will cause immune rejection responses (IRRs), especially in immunocompetent large animals. Therefore, a universal technique needs to be established to overcome IRRs for allogenic cartilage regeneration in large animals. In the current study, a hybrid synthetic-natural electrospun thermoplastic polyurethane/gelatin (TPU/GT) semipermeable membrane to explore the feasibility of stable allogenic cartilage regeneration by an immunoisolation strategy is developed. In vitro results demonstrated that the rationally designed electrospun TPU/GT membranes has ideal biocompatibility, semipermeability, and an immunoisolation function. In vivo results further showed that the semipermeable membrane (SPM) efficiently blocked immune cell attack, decreased immune factor production, and cell apoptosis of the regenerated allogenic cartilage. Importantly, TPU/GT-encapsulated cartilage-sheet constructs achieved stable allogeneic cartilage regeneration in a goat model. The current study provides a novel strategy for allogenic cartilage regeneration and supplies a new cartilage donor source to repair various cartilage defects.
Adjunctive Cariprazine for the Treatment of Patients With Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study
Authors: Gary S. Sachs, Paul P. Yeung, Ludmyla Rekeda, Arifulla Khan, Julie L. Adams, Maurizio Fava
Journal: American Journal of Psychiatry (2023)

The purpose of this study was to investigate the efficacy of cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, as adjunctive therapy for patients with major depressive disorder and nonresponse to at least one antidepressant monotherapy.In this double-blind placebo-controlled study, adults with major depressive disorder and inadequate response to antidepressants alone were randomized in a 1:1:1 ratio to placebo, cariprazine at 1.5 mg/day, or cariprazine at 3.0 mg/day. The primary outcome was change from baseline to week 6 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS). Least-squares mean differences were estimated in the modified intent-to-treat (mITT) population using a mixed-effects model for repeated measures with adjustment for multiple comparisons.The mITT population comprised 751 patients (placebo: N=249; cariprazine 1.5 mg/day: N=250; cariprazine 3.0 mg/day: N=252). At week 6, the mean reduction from baseline in MADRS total score was significantly greater with cariprazine 1.5 mg/day than with placebo (-14.1 vs. -11.5) but not with cariprazine 3.0 mg/day (-13.1). Significant differences between the cariprazine 1.5 mg/day and placebo groups were also observed at weeks 2 and 4. Meeting the MADRS response criteria was significantly more likely among patients receiving cariprazine 1.5 mg/day than placebo (44.0% vs. 34.9%); remission rates were not significantly different among groups. Common treatment-emergent adverse events (≥5% in either cariprazine group and twice the placebo rate) were akathisia and nausea.Adjunctive cariprazine at 1.5 mg/day demonstrated efficacy in reducing depressive symptoms in adults with major depressive disorder and inadequate response to antidepressants alone. Cariprazine was generally well tolerated, with a safety profile that was consistent with previous findings.
Distinct Mutagenic Activity of APOBEC3G Cytidine Deaminase Identified in Bladder Cancer
Authors: Deborah Caswell, Charles Swanton
Journal: Cancer Research (2023)

Abstract The APOBEC cytidine deaminase enzyme family is linked to mutational signatures identified in cancer. While previous work has provided insights into the role of APOBEC3A and APOBEC3B in mutational processes in cancer, understanding of the mutational signatures induced by other APOBEC family members is limited. In this issue of Cancer Research, Liu and colleagues investigated the role of APOBEC3G (A3G) in bladder cancer. The authors revealed that transgenic expression of A3G in a murine bladder cancer model promotes tumorigenesis and induces a unique mutational signature distinct from previously identified APOBEC signatures. Expression of this A3G-related mutational signature correlated with significantly worse survival in patients with urothelial bladder carcinoma, and A3G expression was identified in 21 different cancer types. These findings suggest that different APOBEC3 enzymes induce unique mutation signatures and play distinct roles in cancer evolution. More complete understanding of the function of each APOBEC3 enzyme will improve anticancer therapy. See related article by Liu et al., p. 506
Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Authors: Erika Yue Lee, Christopher Knox, Elizabeth Jane Phillips
Journal: JAMA Dermatology (2023)

Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN.To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide.The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022.Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN.Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs.Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%). There was a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series.In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.
The rise in thick melanomas: can early detection reduce the burden?
Authors: Catherine M Olsen, Nirmala Pandeya, David C Whiteman
Journal: British Journal of Dermatology (2023)

We sought to describe trends in the incidence of invasive melanoma by histological subtype and thickness in two populations with different approaches to the early detection of melanoma (the US White population and Queensland, Australia). The incidence of thick melanoma (&amp;gt; 4.00 mm) increased over the period 1999–2018 at a faster rate than thinner melanomas in both populations, and the increase was driven primarily by increases in melanoma of the nodular subtype. Thin melanomas (&amp;lt; 1.00 mm) were overwhelmingly of the superficial spreading subtype, whereas thick melanomas (&amp;gt; 4.00 mm) were dominated by nodular melanomas.